Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis

Iacovelli, Roberto; Nolè, Franco; Verri, Elena; Renne, Giuseppe; Paglino, Chiara; Santoni, Matteo; Rocca, Maria Cossu; Giglione, Palma; Aurilio, Gaetano; Cullurà, Daniela; Cascinu, Stefano; Porta, Camillo

doi:10.1007/s11523-015-0392-7

Cited by 162 publications

(115 citation statements)

References 32 publications

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“…If this axis is of functional relevance, one might assume that PD1/PD-L1 expression is negatively associated with outcome or with parameters of severe prognosis. In fact, several studies identified such association, at least in ovarian cancer, breast cancer, melanoma, lung cancer as well as in sarcoma [19,[28][29][30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, while PD-1 expression frequently was analyzed, the knowledge about PD-L1 expression as well as its prognostic impact in RCC is still limited and in part contradictory [15][16][17][18][19][20]. To further elucidate the pattern of PD-L1 expression in ccRCC, as well as to understand its prognostic impact, we analyzed intratumoral PD-L1 expression in a retrospective cohort of ccRCC specimens.…”

Section: Introductionmentioning

confidence: 99%

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Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC)

et al. 2016

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The immunological checkpoints of programmed death 1 and its ligand (PD-L1) are currently in focus as novel therapeutic targets in renal cell carcinoma (RCC). The aim of this study was to evaluate the prognostic association of PD-L1 expression in clear cell (cc) RCC with clinical parameters, tumor aggressiveness and overall survival (OS). Patients who underwent renal surgery due to RCC between 1994 and 2003 were retrospectively evaluated. Tumor specimens were analyzed for PD-L1 expression by immunohistochemistry. One hundred and seventy-seven ccRCC patients were eligible for analysis, in which 140 (79.1 %) were negative and 37 (20.9 %) were positive for PD-L1 expression. PD-L1 positivity was associated with female gender (p = 0.001), lymph node metastasis (p = 0.004), distant metastasis (p = 0.002), higher AJCC stage (p = 0.004), as well as advanced disease (pT3/4 and/or N+ and/or M1) (p < 0.001). Kaplan-Meier analysis revealed a significantly diminished 5- and 10-year overall survival of 46.7 and 28.3 % for PD-L1(+) compared to PD-L1(-) tumors with 66 and 53.4 % (p = 0.005), respectively. Univariate analysis showed a significant negative association of OS with PD-L1 positivity [p = 0.005; HR: 2 (95 % CI 1.2-3.3)], even though PD-L1 positivity only tends to predict independently the OS using multivariate analyses [p = 0.066; HR: 1.6 (95 % CI 0.98-2.7)]. PD-L1 expression in ccRCC is associated with parameters of aggressiveness, as well as with poor OS, even though PD-L1 status was not identified as a significant independent prognostic parameter. However, further studies in larger cohorts are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC)

et al. 2016

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“…31 In another meta-analysis of RCC, high level of PD-L1 expression was a negative prognostic factor that increased the risk of death by 81% (hazard ratio, 1.81; 95% CI, 1.31-2.49; P , .001). 33 In gastric carcinoma, PD-L1 expression by immunohistochemistry was associated with larger tumor size, invasion into the deep muscular layers, lymph node metastasis, and decreased survival time of patients (,2 years). 34 Moreover, multivariate analysis demonstrated that PD-L1 immunodetection could be used as an independent factor to evaluate the prognosis of gastric carcinoma.…”

Section: Pd-1/pd-l1 Expression As a Prognostic Marker In Various Cancersmentioning

confidence: 92%

“…However, a few studies revealed that expression of PD-L1 in tumor cells may imply better prognosis. Additionally, several studies beyond those noted in Table 1 showed that PD-L1 expression in tumor cells and tumor-infiltrating lymphocytes is correlated with poor prognosis in such cancers as NSCLC, 31 melanoma, 32 RCC, 33 and esophageal and gastric cancers. 34 A meta-analysis conducted by Wang et al 31 in 1157 patients with NSCLC showed that PD-L1 expression was significantly associated with poor differentiation of tumors (poor versus well: odds ratio, 1.91; 95% CI, 1.33-2.75; P ¼ .001) and with worse overall survival (pooled hazard ratio, 1.75; 95% CI, 1.40-2.20; P , .001).…”

Section: Pd-1/pd-l1 Expression As a Prognostic Marker In Various Cancersmentioning

confidence: 98%

Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers

Guan¹,

Lim

Mekhail³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1–targeted therapy in various cancers and reveal a new era of cancer immunotherapy. Objective.— To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression. Data Sources.— Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16–20, 2016). Conclusion.— Either PD-1/PD-L1–targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1–targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1–targeted therapy.

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“…Among the first studies in patients undergoing nephrectomy, expression of PD-L1 was associated with a hazard ratio (HR) of 4.5 (95% confidence interval (CI) 1.94-10.56; p < 0.001) for death [18]. More recently, a meta-analysis of 6 studies revealed that PD-L1 expression is found in 24% of clear cell RCC and in only 11% of non-clear cell RCC specimens (p = 0.002) [19]. High PD-L1 expression levels were associated with risk of death (HR 1.81; 95% CI 1.31-2.49; p < 0.001), and this impact on prognosis was maintained in patients with metastatic disease.…”

Section: The Prognostic Role Of Checkpoints In Rccmentioning

confidence: 99%

Checkpoint Blockade - a New Treatment Paradigm in Renal Cell Carcinoma

Grünwald

2016

Oncol Res Treat

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Nivolumab is the first checkpoint inhibitor for the treatment of renal cell carcinoma (RCC), which is in line for approval in Europe. Despite its novelty in the treatment algorithm of RCC, it offers a whole new strategy of therapy management with safe applicability. The aim of this work was to review current data on checkpoint inhibitors in RCC and discuss future perspectives for this novel approach in RCC. A selective literature search was performed in the Pubmed database: Nivolumab is a first-in-class agent for the treatment of RCC, and its European label is anticipated for 2016. Contrary to many other agents, nivolumab was able to show a benefit in overall survival and health-related quality of life when compared to everolimus. Current trials focus on optimizing and expanding its use to metastatic RCC. In conclusion, nivolumab has already acquired a role in the treatment algorithm of RCC. However, which patient population derives the most benefit as well its optimal use in the treatment algorithm remain to be determined. A number of ongoing trials will provide novel insights and might help to untangle this novel network of therapy management for immunotherapies.

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Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis

Abstract: This meta-analysis indicates that a higher level of PD-L1 expression is a negative prognostic factor in RCC. Its validation as an independent prognostic factor compared to other traditionally used clinical parameters in localized or advanced disease is recommended.

Cited by 162 publications

References 32 publications

Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC)

Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC)

Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers

Checkpoint Blockade - a New Treatment Paradigm in Renal Cell Carcinoma

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